CGTLive's Pillars of Progress 2023: Top News in Neurology

For all of 2023, the CGTLive^™ team was following along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page.

Among our areas of focus in 2023 has been neurology. This year bore witness to the landmark approval of the first Duchenne muscular dystrophy (DMD) gene therapy by the FDA, and many other gene and cell therapies for neurological indications made progress in the pipeline. The major news items appeared among the top pieces our team produced—but sometimes smaller stories reach those heights as well because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in neurology over the course of 2023.

Here, we'll highlight some of the most-read content on CGTLive's neurology page this year. Click the buttons to read further into these stories.

1. FDA Approves Sarepta's Landmark DMD Gene Therapy Elevidys

• Delandistrogene moxeparvovec uses the AAVrh74 recombinant vector to express microdystrophin.
• The biologics license application was supported by data from the global, randomized, double-blind, placebo-controlled phase 3 EMBARK clinical trial (NCT05096221).
• The FDA has noted that it may consider a non–age-restricted expansion of the therapy’s label if EMBARK ultimately meets its objectives.

June 22, 2023 — The FDA has approved Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001) for treating ambulatory pediatric patients aged 4 through 5 years with DMD and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9, to be marketed under the name Elevidys.

"It is gratifying and a relief to finally have an approved gene therapy for DMD. This drug is likely to be the most potent treatment method available today, although it is not as robust as many had hoped."

– Jeffrey Chamberlain, PhD, of University of Washington School of Medicine

2. Limb-Girdle Muscular Dystrophy Gene Therapy Gets EC Orphan Drug Designation

• AB-1003 is delivered as a single dose via intravenous infusion.
• AB-1003 previously received clearance of its investigational new drug application from the FDA in May 2021.
• Soon after, in June 2021, AB-1003 was granted fast track designation by the FDA.

March 3, 2023 — Asklepios BioPharmaceutical (AskBio)’s AB-1003 (LION-101), an investigational adeno-associated virus (AAV) vector-based gene therapy currently being evaluated for the treatment of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) in a phase 1/2 clinical trial (NCT05230459), has received orphan drug designation from the European Commission (EC) through AskBio’s Europe-based subsidiary, BrainVectis.

"The EC orphan drug designation for AB-1003 is an important recognition of the unmet medical need in LGMD, which has no approved therapy."

– Sheila Mikhail, of AskBio

3. Patient With Parkinson Disease to Receive Compassionate Use of NK Cell Therapy

• SNK01 is the subject of a collaboration between NKGenBitoech and the Parkinson’s Foundation minted in November 2022.
• The collaboration is focusing on ways to help accelerate the development of SNK01 for the treatment of advanced PD through its network of clinical partners and donors.
• SNK01 is an autologous, NK cell therapy. It is NKGen’s lead candidate and is also currently being assessed in clinical trials for the treatment of advanced refractory solid tumors both as a monotherapy and in combination with other agents, including checkpoint inhibitors and cell engagers.

March 5, 2023 — The FDA has approved NKGen Biotech’s natural killer cell (NK) therapy SNK01 for compassionate use in treating a patient with Parkinson disease (PD). NKGen is the American branch of Korean company NKMAX.

“We are looking to support novel innovative approaches in PD, and we are attracted to NKGen’s unwavering commitment to bring their NK cell therapy to the clinic very quickly.”

– John L. Lehr, of Parkinson’s Foundation

4. Rett Syndrome Gene Therapy Cleared for Clinical Trial

• NGN-401 is an AAV gene therapy that uses Neurogene’s proprietary gene regulation platform technology Expression Attenuation via Construct Tuning (EXACT) that was developed in collaboration with the University of Edinburgh.
• EXACT is meant to address toxicities and limitations with conventional gene therapy and is compatible with both viral and non-viral delivery methods.
• The therapy delivers the full-length human MECP2 gene, expression of which is regulated by EXACT to avoid overexpression-related toxicities.

January 24, 2023 — The FDA has cleared Neurogene’s investigational new drug application of NGN-401 and the company is planning to initiate a phase 1/2 clinical trial to evaluate intracerebroventricular (ICV) injection of the gene therapy in girls with Rett syndrome in 2023.

“Rett syndrome is a particularly challenging disorder for gene therapy because of the requirement to deliver therapeutic levels of MECP2, without also triggering significant side effects associated with too much gene expression.”

– Rachel McMinn, PhD, of Neurogene

5. Parkinson Disease iPSC-derived Therapy ANPD001 Cleared for Clinical Trial in the US

• ANPD001 consists of dopamine neuronal precursor cells (DANPCs) produced from iPSCs that are in turn derived from samples of patients’ own skin cells.
• ANPD001 is implanted surgically and is intended to replace dopamine neurons that have been damaged or destroyed by the disease.
• Aspen noted that it will use a set of proprietary artificial intelligence-based whole genome sequencing and RNA sequencing tests to check for mutations and downstream functionality for the main stages of the therapy’s manufacturing process.

August 12, 2023 — Aspen Neuroscience has received clearance from the FDA for an investigational new drug (IND) application for ANPD001, an investigational autologous induced pluripotent stem cell (iPSC) derived therapy intended to treat PD.

“The IND clearance of ANPD001 sets in motion a path toward a new treatment for the more than 1 million Americans and 10 million people worldwide with PD."

– Damien McDevitt, PhD, of Aspen Neuroscience